Derivatives of organic arsenic compounds



AUGUST ALBERT, or Monica, enrol/raisin No Drawing. Application filed March' 25,

T 0 all whom it may concern.

Be 1t known that. I, AUGUST ALBER a citizen of the Republic of Germany, and residing in Munich, Elisabethstrasse 46, Germany, have invented new and useful Derivatives of Organic Arsenic Compounds, ,of which the following-is a specification.

It is known that the aromatic compounds, I

containing carbonyl groups, do not respond to certain carbonyl reactions, for instance the bisulphite reaction which otherwise is often used for separating and isolating the aldehydeand keto-compounds. Also the efiort to acetylize these compounds is found to be negative. Even the semi-carbazide reaction does not proceed in many cases, for instance p-benzophenoarsonic acid is indifferent, or is reduced in an undesired manner. Attempts to produce biologically effective hydrazine compounds of the said arsenic derivatives therefore appeared hopeless.

Now I have found that mixed aliphatic aromatic carbonyl arsenic compounds react smoothly with hydrazine and the various hydrazine derivatives without undesirably reducing the carbonyl groups -which are known to be reduced easily. This effect could the less be foreseen because the hydrazine compounds are known to possess a very strong reducing effect and it was therefore not'to be expected that the desired hydrazine reaction would occur, and also because it was possible that undesirable side reactions would occur. I 7

By the term mixed aliphatic aromatic carbonyl arsenic compounds are to be understood compounds of the class R C::OR in which R, is hydrogen or any alkyl group or substituted alkyl group, either saturated or unsaturated and R is the arsenic or arsonic acid derivative of a simple aromatic radical such as 0 H or of a polynuclear or condensed nuclear radical,

simple or substituted, carbocyclic or heretocyclic. It is to be especially noted that the carbonyl group may be attached directly to the aromatic nucleus or to a side chain thereof.

As'examples of the carbonyl compounds in which the carbonyl group is attached directly to the aromatic nucleus DERIVATIVES OF ORGANIC ARSENIC COMPOUNDS.

1922. Serial No.. 546,792.

loxy-acetophenon l-arsonic acid As examples of carbonyl compounds in which the carbonyl group is attached to a side chain of the aromatic nucleus may be mentioned the following:

I, I I I k/--C 200GB?- Specification of Letters Patent. Patented A 15 1922 Y may be-men-:'

To carry out the desired reaction it is suf ficient to mix the reagentsinqeither acid, alkaline or neutral medium. It is easy'to determine by trial What medium gives the optimum yield in any partciular case. The hydrazine used" may be s implel hydrazine, N H NH or monosubstituteduhydrazine NH NHR or asymmetric disubstituted a hvdrazme H N-N 1 u 2 \R Under R and R i espectively, are under-c ,1

stood aliphatic or aromatic or mixed aliphatic aromatic radicals of radicals with other hydrazine complexes.

each kind; or

The bodies produced according to the described process are generally well defined loath. The phenylhydrazine may be crystallized out of glacial acetic acid. It

v and: p-nitrophenylhydrazine;

chaeta pallida and the like and are found useful in therapeutics.

Ewamples.

1. 1 gram p-acetophenonarsonic acid is dissolved in 8 com. 3 normal sodium carbonate lye and 1 com. of 50% hydrazine hydrate solution is added. After standing quietly for a time, hydrochloric acid is added and the hydrazone I v .G 3

, ASO.(OH)'J separates as a nearly colorless product. When dried in vacuo and heated in a capil lary tube to a temperature above 340 C. it shows a slight darkening Without melting.

2. To a solution of 4: g p-acetophenoarsonic acid in 40 com. of 50% acetic acid is added 2 com. phenylhydrazine. After standing, the yellow phenylhydrazine separates. To complete'the reaction the mixture is placed for some time on the Water forms light yellow plates Which decompose at a temperature of 225;

3. In the same manner the p-nitrophenylhydrazone of the 1-oXy-Q-propionphenon4l A'so oH)z is formed from the 1-oxy2-propionphenon- 4-arson1c acld p Y When recrystallized'out of acetic acid, clusters of -fine pointedylloiv needles are produced Wvhich decompose at'a temperature of 235,

a. The semicarbazone of the 6 (?)-nitroloxy-acetophenon-d-arsomc acid more? \soent I Of the aminobiuret may be recrystallized out of a large amount of 20% acetic acid. It

forms pointed plates Which do not melt below a temperature of 360, but become a yellowish brown color.

6. The amidoguanidine derivative of the p-acetophenonarsonio acid:

is obtained by addition of 2 parts of amideguanidin nitrate (by Weight) to a solution of 5 parts of arsonic acid in 30 com. of normal sodium carbonate solution after a short heating. By careful addition of diluted. hydrochloric acid the amidoguanidin derivative separates out in crystals, .It is soluble in dilute acids in the cold; Heated in the capillary tube the substance. gently decomposes at a temperature higher than 300. L l v 7. The corresponding semicarbazone lemon is formed in. good yield out of p-benzalaca 'tci'u2-: ,raonic acid ,i

CH=CHiCOiCHs and semicarbazidechlorhydrate in hot aqueous solution. It is colored intensely yellow, crystallizes in thick needles and decomposes when heated in the capillary tube above temperature of 330 C. and turns brown.

8. If to an aqueous solution of p-benzaldehydarsonic acid:

COH

the theoretical quantity of asymmetric diethylhydrazine is added, the diethylhydrazone separates on heating as an oil and crystallizes in the cold. When recrystallized out of aqueous alcohol it melts with slow decomposition at 1A0". The diethylhydrazone may be dissolved in diluted hydrochloric acid.

9. 4 parts by Weight of p-benzaldehydarsonic acid in glacial acetic acid solution are heated for some time on the water bath with 1 parts by weight of crude asymmetric methylphenyl hydrazine, the redbrown solution is rapidly evaporated on the water bath after which the addition of water and diluted hydrochloric acid produces crystallized methylphenylhydrazone:

AsO (OH);

Recrystallized out of aqueous acetic acid, the product forms yellow feather shaped masses of needles which melt at a temperature of about 295 .withstrong decomposition.

10. Example for a trivalent arsenic com-.

pound: 0.5 grams 1-arseno-3-oxyl-methyle phenylketone are stirred with 5 com. double normal NaOI-I. Wateris added until the substance is completely dissolved and then 0.3 grams semicarbazidhydrochloride are added. The solution is heated for half an hour on the water bath, preferably with limited contact with air or the solution is left standing a longer time at ordinary temperature and cooled. After addition of dilute hydrochloric acid, the light yellow prodnot is filtered with suction, washedand dried in vacuo, whereby it becomes colored, sometimes light brown. The dry product is soluble in NaOH solution. The boiling points vary according to the method of heating.

-11. 0.5 grams p-acetophenon-arsonic acid are dissolved in 4: ccm. normal NaOH (about 1 mol. NaOH) or sodium carbonate and to the clear solution J; mol. carbohydrazide 0.1 g. is added. The transforma tion begins in the cold. It is suitable to let the solution stand for 24 hours and then to separate the white crystalline carbohydrazide derivatives by means of 2 com. normal hydrochloric acid, from the clear solution. It may be heated almost unchanged in a capillary tube to 360 C. It shows the well known magnesia reaction of the arsonic acids in concentrated ammoniacal solution even in the cold. r r

12. 0.5 grams p-acetophenonarsonic acid are dissolved as'above mentioned and then 0.13 grams malonylhydrazide added to the by heating for a short time on the water bath. To. complete the reaction the solution should stand for a few hours at'ordinary temperature and then the-hy'drazone isseparated with 2 ccm. HCl. 360 (3., it shows little change. I

13. 0.5 grams p-acetophenon-arsonic acid are dissolved and 0.12 grams oxalylhydrazide.

added. After heating half an hour on the Heated to about solution. The transformation is accelerated water-bath,the reaction is nearlycomplete.

in which As represents pentavalentarsenic,

It represents hydrogen or an alkyl' group, R represents a phenyl group, and R represents "a group containing a hydrazine nucleus.

' 2. As a new composition of matter, the hydrazone of methyl, phenol ketone having an. arsenic acid group attached to the aro-' matic nucleus.

Witnesses:

ALEXANDER on So'ro, ALEXA V. PHILIBPQFF.

AUGUST ALBERT. 7

Certificate of Correction.

It is hereby certified that in Letters Patent No. 1,425,929, granted August 15, 1922, upon the application of August Albert, of Munich, Germany, for an improvement in Derivatives of Organic Arsenic Compounds, errors appear in the printed specification requiring correction as follows: Page 1, line 41, for the Word read m'sz'nic, and lines 44- and 45, for the misspelled Word heretocyclic strike out line 52 and insert the syllable and words and line 1, page 3, in the formulas, for

arsenic read heterocyclz'c; same page, toned the following; and line 92, page 1, the sign 1 read page 2, line 55, in the formula, strike out the dash between C and O and insert a double bond; and that the said Letters Patent should be read with these corrections therein that the same may conform to the record of the case in the Patent Office. .v

Signed and sealed this 10th day [SEAL] I of October, A. 1)., 1922.

WM. A. KINNAN,

Assistant Conwm'ssioner of Patents. 

